The broad objectives of the project are to characterize the mechanisms which set the accuracy of transcription and translation, including the nucleotide sequence context rules. The accuracy of gene expression may be a factor in senescence, and is apparently modified in certain kinds of neoplastic transformation. It is also a critical matter for the biotechnology industry. Our specific aims are to study a noncognate triphosphate hydrolase activity of RNA polymerase which is apparently involved in proofreading; to define the nucleotide sequence information involved in the maintenance of reading frame; to determine the relationship between aminoacyl-tRNA charging levels and mistranslation frequency; and to determine the nucleotide sequence rules which affect release factor binding.